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Biomedical subjects

T Kasai

Publications and source records attributed to T Kasai.

At least 19 recordsLinked to original sources

Metabolic activation of 2- and 3-nitrodibenzopyranone isomers and related compounds by rat liver S9 and the effect of S9 on the mutational specificity of nitrodibenzopyranones.

The effect of rat liver S9 on the mutagenicity of 10 nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) was evaluated with Salmonella typhimurium TA98NR using S9 from phenobarbital-, 3-methylcholanthrene (MC)-, beta-naphthoflavone- and polychlorobiphenyl-treated and untreated rats. 2-Nitrofluorene (2-NFI), 2-nitrofluoren-9-one (2-NFlone), 2-nitrocarbazole (2-NCz), 3-NCz, 2-nitrodibenzothiophene (2-NDBT), 2-nitro-6H-dibenzo[b,d]pyran-6-one (2-NDBP) and 3-NDBP were metabolically activated by one or more of the S9 fractions, and the highest enhancement of the mutagenic potency of nitro-PAHs was observed with 3-MC-induced S9. Only in the case of 3-NFlone was the mutagenicity in strain TA98NR decreased by the addition of S9, regardless of S9 induction. 2-NDBP was most efficiently activated among nitro-PAHs tested by all S9 fractions used. The cytosolic fraction of S9 accounted for more of the activation of 2-NDBP than the microsomal fraction. NADH and NADPH were the most effective electron donors on the activation of 2-NDBP by S9, 2-NDBP was also metabolically activated by NADH plus commercial preparations of xanthine oxidase. These activations of 2-NDBP were inhibited by allopurinol, indicating that cytosolic xanthine oxidase in rat liver S9 participates in the activation of 2-NDBP. The potency of 2- and 3-NDBP isomers as base-substitution mutagens was also enhanced by S9. In the presence of S9, both compounds showed the highest mutagenicity in strain TA7005 (C.G-->A.T) followed by strains TA7004 (G.C-->A.T), TA7006 (C.G-->G.C) and TA7002 (T.A-->A.T), and this mutation specificity was similar to that without S9, indicating that the mechanism of mutagenesis caused by NDBP isomers with S9 is similar to that without S9.

Animals

Evidence for facilitation of motor evoked potentials (MEPs) induced by motor imagery.

This study examined the extent to which motor imagery can facilitate to specific pools of motoneurons. Motor commands induced by motor imagery were subthreshold for muscle activity and were presumably not associated with any change in background afferent activity. To estimate excitability changes of flexor carpi radialis (FCR) muscle motoneuron in spinal and cortical level, electric stimuli for recording H-reflex and transcranial magnetic stimulation (TMS) for recording motor evoked potentials (MEPs) were used. During motor imagery of wrist flexion, remarkable increases in the amplitude of the MEP of FCR were observed with no change in the H-reflex. Furthermore, facilitation of antagonist (extensor carpi radialis; ECR) was also observed. Therefore, it is concluded that internal motor command can activate precisely cortical excitability with no change in spinal level without recourse to afferent feedback.

Adult

Growth of the cervical spine with special reference to its lordosis and mobility.

STUDY DESIGN: The cervical spine of the healthy Japanese children aged between 1 year and 18 years was radiographically examined. OBJECTIVES: To examine the correlation between growth of the cervical vertebral body and the facet joint and the development of the cervical lordosis and intervertebral motion. SUMMARY OF BACKGROUND DATA: Although the growth of body height and facet angle have been well documented, their correlation with curvature or mobility has not been elucidated. METHODS: We evaluated plain lateral radiographs of 180 boys and 180 girls regarding diameters and central heights of the cervical vertebra, the anterior and posterior vertebral height ratio, body height index, the facet joint angles, and tilting and sliding motions. Cervical length as the summation of the central height from C3 to C7 and the cervical lordosis angle (C3-C7 angle) were also measured. RESULTS: The mean C3-C7 angle and body height index gradually decreased until 9 years of age and then increased. The C3-C7 angle showed a significant correlation with cervical length, body height index, and facet joint angles before 9 years of age, and with cervical length and body height index after 9 years of age but not with facet joint angles. Facet joint angle decreased until 10 years of age and remained almost unchanged thereafter. Total sliding showed a significant age-related decrease and showed a significant correlation with facet joint angle. CONCLUSION: Although the lordosis angle showed a significant correlation with the other values, cervical length, body height index, and facet joint angle, the determinants of the lordosis could not be elucidate in the present study. As for the mobility of the cervical spine, changes of tilting motion were small, whereas changes of sliding motion were restricted by the change of orientation of the facet joints.

Adolescent

Genotoxicity in vivo of phenazine and aminophenazines assayed in the wing spot test and the DNA-repair test with Drosophila melanogaster.

The genotoxicity and DNA-damaging activity of 6 phenazine and aminophenazine derivatives were assayed in the wing spot and DNA-repair tests in Drosophila melanogaster. Phenazine (Pz), and all aminophenazines tested, namely, 1-aminophenazine (APz), 2-APz, 2,3-diaminophenazine (DAPz), 2,7-DAPz and 2,7-diamino-3,8-dimethylphenazine (DADMPz), exhibited mutagenicity significantly in the wing spot test. The activities in the wing spot test were ranked in a sequence DADMPz > (2,7-DAPz, 2,3-DAPz) > (2-APz, 1-APz, Pz). In the DNA-repair test, 2,3-DAPz, 2,7-DAPz, and DADMPz clearly showed DNA-damaging activity, but Pz, 1-APz and 2-APz were inactive. Based on these results, we predict that DADMPz, 2,3-DAPz and 2,7-DAPz are likely to be more carcinogenic than 2-APz, 1-APz or Pz.

Animals

Construction of gene expression system in cultured tobacco cells.

To construct a gene expression system in cultured tobacco cells, useful regulatory elements of plant genes were studied. The promoter of the horseradish peroxidase gene, prxC2, showed high activity in tobacco cells, and it contained enhancer sequences and a cis element for wound induction. The heat shock promoter of the HSP18.2 gene from A. thaliana had strong activity of transcription when the incubation temperature of tobacco cells was shifted from 25 degrees C to 37 degrees C. These elements could be good candidates for foreign gene expression in tobacco cells.

Arabidopsis

Soleus H-reflex depression induced by ballistic voluntary arm movement in human.

A biomechanical and neurophysiological analysis of anticipatory postural adjustments associated with the early phase of a voluntary arm movement was carried out in normal human subjects. Arm elevation, performed at maximal velocity, was studied with unilateral arm movement in freely and counterbalanced (suspended in a safety harness) standing humans. The ground reaction force of both legs, tangential acceleration of the shank and electromyographic activity (EMG) of the anterior deltoid (AD), biceps femoris (BF) and soleus (Sol) muscles were recorded. Sol H-reflexes of both legs were also elicited. To examine how the Ia inhibitory and presynaptic inhibitory pathways are related to anticipatory postural adjustments, additional Sol H-reflexes were elicited using the classical conditioning-test technique (time interval 2 and 15 ms, respectively). In this study, we systematically described biomechanical and EMG phenomena that precede and follow the onset of voluntary arm movements. Prior to and during the arm movement (i.e. AD activation), a sequence of EMG modifications occurred in ipsilateral BF and Sol muscles. Those modifications preceding BF activation included silent phases in Sol EMG and depression of Sol H-reflexes. By comparing EMG modifications with depressions of the Sol H-reflex, we conclude that Ia and presynaptic inhibitory pathways do not play a specific role in those Sol H-reflex depressions. Moreover, because Sol H-reflex depression occurs in both freely standing and counterbalanced postures, anticipatory postural adjustment appear to be preprogrammed in the central nervous systems unrelated to peripheral neural mechanisms. Since changes of EMG activities of ipsilateral BF and Sol appeared simultaneously and Sol H-reflex depressions were dependent on EMG activities of ipsilateral BF, control commands to anticipatory postural adjustment would excite BF and inhibit Sol.

Adult

Increases in calcium absorption with ingestion of soluble dietary fibre, guar-gum hydrolysate, depend on the caecum in partially nephrectomized and normal rats.

Effects of feeding soluble dietary fibre on apparent Ca absorption and the contribution of the caecum to Ca absorption were examined in five-sixths nephrectomized (NPX) and normal rats with or without caecectomy in four experiments. It is known that Ca absorption is lowered by renal failure. In the first experiment the amounts of femur Ca increased linearly with increasing dietary Ca up to 3.0 g Ca/kg diet in intact rats. Partial nephrectomy decreased apparent Ca absorption in rats fed on diets containing 3-0 and 4.5 g Ca/kg diet. In the NPX groups, Ca absorption in rats fed on the diet containing guar-gum hydrolysate (GGH; 50 g/kg diet; 3.0 g Ca/kg diet) was significantly higher than that in rats fed on a fibre-free diet, and the increase in Ca absorption with GGH feeding was completely abolished by caecectomy. Also, ingestion of GGH increased Ca absorption in normal rats, but not in normal, caecectomized rats. Mg absorption was also increased with GGH feeding and was decreased with caecectomy in NPX and normal rats. In experiments which used caecectomized rats, coprophagy was prevented with an anal cup to avoid re-ingestion of faecal Ca. We conclude that ingestion of the soluble dietary fibre, GGH, increased apparent Ca absorption in NPX and non-NPX rats, and the caecum was responsible for these increases in Ca absorption.

Animals

Human T lymphocyte virus type I-induced myeloneuropathy in rats: implication of local activation of the pX and tumor necrosis factor-alpha genes in pathogenesis.

The pathogenetic roles of human T lymphocyte virus type I (HTLV-I) and cytokines were investigated in HTLV-I-induced myeloneuropathy in Wistar-King-Aptekman-Hokudai rats. In the nervous system, pX messenger RNAs of HTLV-I were selectively expressed in the diseased spinal cord and peripheral nerves but not in the unaffected cerebrum and cerebellum, even though proviral DNAs were consistently identified in these tissues. Among several cytokines examined, mRNA expression and production of tumor necrosis factor (TNF)-alpha in the spinal cord and cerebrospinal fluid correlated positively with the development of spinal cord lesions. The collective evidence strongly suggests that selective activation of HTLV-I, in particular Tax expression and production of TNF-alpha induced by HTLV-I infection in target spinal cord and peripheral nerves, is causally related to apoptotic death of oligodendrocytes and Schwann cells, a major pathogenetic pathway of the HTLV-I-induced myeloneuropathy.

Animals

Oxidized ethyl linoleate induces mucosal hypertrophy of the large intestine and affects cecal fermentation of dietary fiber in rats.

Oxidized ethyl linoleate (OEL) was prepared by aeration at low temperature. Peroxide value (POV, mEq/kg lipid) of OEL was 1400; the major oxidized compounds were 9-hydroperoxy-cis, trans- and 13-hydroperoxy-trans, cis-octadecadienoate. Rats fed fiber-free or sugar-beet fiber (SBF, 100g/kg diet) diets were divided into three groups for each diet, and administered OEL (high OEL group), OEL diluted with ethyl linoleate (low OEL group, POV 700) and nonoxidized ethyl linoleate (EL group) through gastric tubes each day at 1400-1600 h (2.5 g/kg body wt) for 16 d. The relative wet weight, and DNA and protein contents of the cecal mucosa were higher in the high OEL groups than in the low OEL and EL groups in rats fed the fiber-free diet and in rats fed the SBF diet except for mucosal protein content. Spermidine concentration in cecal mucosa of rats fed the fiber-free diet was greater in the high OEL group than in the EL group. These results suggest that metabolism related to mucosal proliferation of the cecum was affected by the high dose of OEL. The total short-chain fatty acid (SCFA) concentration in the cecal contents of SBF-fed rats was 100% higher than the concentration in rats fed the fiber-free diet in the EL group, but the administration of low dose and high dose OEL lowered the SCFA concentration in fiber-fed rats to that of rats fed the fiber-free diet. Butyric acid concentration was markedly lowered by ingestion of OEL in a dose-dependent manner in rats fed the SBF diet. In contrast, the isobutyric acid concentration was higher in the OEL-treated groups than in the EL groups. We conclude that a low dose of OEL depresses cecal fermentation of dietary fiber with changes in SCFA composition, and that a high dose of OEL induces mucosal hypertrophy in the cecum. These data show that dietary oxidized lipids affect cecal metabolism and may be associated with colon cancer.

Animals

Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis.

The hypothesis that dietary branched-chain amino acid (BCAA) supplementation improves the impaired protein turnover in male Donryu rats with carbon tetrachloride-induced liver cirrhosis was tested. We supplemented cirrhotic rats orally for 2 wk with BCAA solution [26.67 mg BCAA/(100 g body weight . d)], a conventional amino acid mixture [4.25 mg BCAA/(100 g body weight . d)] or saline and fed these three groups the AIN76 basal diet to have similar intakes of total energy and total nitrogen. Normal rats without liver cirrhosis were fed the basal diet similar to the above (noncirrhotic controls). After supplementation, rats were fed intravenous transthyretin (thyroxine-binding prealbumin) doubly labeled with 125I-tyramine-cellobiose and 131I. Kinetic indices including production rate of transthyretin were analyzed from plasma transthyretin disappearance curves. Tissue sites of transthyretin degradation were assayed using a trapped ligand technique by measuring 125I-tyramine-cellobiose levels. The production rate of transthyretin was significantly lower in cirrhotic rats supplemented with saline (mean 25.46 X 10(-3) . h(-1)) compared with noncirrhotic controls (45.08 X 10(-3) . h(-1)) (P < 0.05). This was corrected by supplementing cirrhotic rats with BCAA (37.05 X 10(-3) . h(-1), P < 0.05) but not with conventional amino acid mixture (22.49 X 10(-3) . h(-1)). The accelerated degradation of transthyretin in muscles of cirrhotic rats was improved by BCAA (P < 0.05). In conclusion, dietary supplementation with BCAA improves the impaired transthyretin turnover in rats with liver cirrhosis.

Administration, Oral

Retrospective analysis of the treatment of patients with small cell lung cancer showing poor performance status.

To assess the feasibility of treatments for patients with small cell lung cancer (SCLC) showing a poor performance status (PS, Eastern Cooperative Oncology Group; ECOG 3 or 4), we retrospectively reviewed the outcome for 13 SCLC patients showing poor PS treated at the National Cancer Center Hospital between January 1984 and May 1994. The main factors which contributed to poor prognosis were superior vena cava (SVC) syndrome, massive pleural effusion, tracheal stenosis due to lymph node swelling, pericardial effusion and pulmonary fibrosis (causing dyspnea in combination), brain metastasis resulting in neurological disturbance, cachexia, Eaton-Lambert syndrome causing muscle weakness, retroperitoneal lymph node metastasis causing abdominal pain, peritoneal effusion due to abdominal lymph node swelling, vertebral metastasis causing paraplegia, and dermatomyositis/polymyositis (DM/PM) causing muscle weakness. All of the patients received chemotherapy with or without radiotherapy. The PS of 8 patients improved with treatment, but no improvement was seen in 5. We analyzed these 13 patients and considered the treatments for those with poor PS. Chemo-radiotherapy was tolerable in SCLC patients showing PS 3, and improved their PS if severe conditions or combined disease did not arise concurrently. It was further suggested that PS 4 patients with severe conditions or combined disease should not be given the treatments.

Adult

Epstein-Barr virus-associated gastric carcinoma.

Epstein-Barr virus (EBV) is associated with certain types of gastric carcinoma. We report a case of EBV-positive undifferentiated carcinoma of the stomach in a 59-year-old woman with a well-demarcated ulcerating tumor in the gastric body. Examination of the resected stomach revealed that the tumor was undifferentiated carcinoma with lymphoid stroma, or lymphoepithelioma-like carcinoma. Tumor cells were positive for EBV by in situ hybridization. Gastroenterologists must keep in mind that localized ulcerating tumors of the stomach histologically seen as undifferentiated carcinnoma with lymphoid stroma are linked to EBV infection.

Carcinoma

CK-independent increases in pancreatic secretion induced by dietary protein in chronic BPJ-diverted rats.

Previously, we demonstrated that, in rats with chronic bile-pancreatic juice (BPJ) diversion, pancreatic enzyme secretion was increased after feeding animals a 25% casein fat-free diet. We determined whether cholecystokinin (CCK) or the cholinergic pathway is associated with the response of pancreatic secretion after protein ingestion in the diverted rats, using a potent CCK antagonist, MK-329 or FK-480, and a cholinergic blocker, atropine. Secretion rates of chymotrypsin and trypsin in the fasting state were very high 7 days after a BPJ diversion, and the hypersecretion of the proteases was markedly reduced with an injection of MK-329, FK-480, or atropine and was further reduced by combined injection of FK-480 and atropine. The lowered secretion of the proteases in CCK-antagonized rats was increased after oral feeding of a protein diet and after a duodenal instillation of some protein sources, especially hydrolysate of guanidinated casein (HGC). The CCK-independent increases by HGC instillation are completely depressed by atropine. In rats treated with only atropine, the lowered secretion tended to be increased by a duodenal instillation of HGC. Increases in secretion after an administration of the protein source in CCK-antagonized rats were not affected by bestatin, an inhibitor of brush-border peptidases. We conclude that the stimulatory effects of dietary protein on the pancreatic enzyme secretion partially do not depend on CCK in chronic BPJ-diverted rats and that the CCK-independent increase is atropine sensitive.

Animals

Inhibitory effect of dietary wheat bran on formation of aberrant crypt foci in rat colon induced by a single injection of 1,2-dimethylhydrazine.

The frequency of appearance of aberrant crypt foci (ACF) in the distal colon was significantly lower in rats fed a high fiber (20% wheat bran) diet than in those fed a fiber-free one at 4 weeks after a single injection of 1,2-dimethylhydrazine (DMH, 20 mg/kg), although crypt/ACF was high in the former relative to the latter. This result suggests that dietary wheat bran effectively serves as a regulator of ACF frequency at early stages after DMH injection.

1,2-Dimethylhydrazine

Impaired pancreatic acinar sensitivity to cholecystokinin but not to carbachol in rats with chronic bile pancreatic juice diversion.

Changes in the sensitivity and responsiveness to CCK and cholinergic stimuli were examined in isolated pancreatic acini prepared from 7-day BPJ-diverted rats. The sensitivity to CCK was lower in BPJ-diverted rats than in the control rats, but the sensitivity to the cholinergic agonist, carbachol, was not changed. These results suggest that the contribution of the cholinergic pathway to pancreatic enhancement by feeding dietary protein can be increased after chronic BPJ diversion.

Animals